Variant 15-66703215-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_005585.5(SMAD6):c.-44C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,318,380 control chromosomes in the GnomAD database, including 333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 19 hom., cov: 33)

Exomes 𝑓: 0.020 ( 314 hom. )

Consequence

SMAD6
NM_005585.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

SMAD6 (HGNC:6772): (SMAD family member 6) The protein encoded by this gene belongs to the SMAD family of proteins, which are related to Drosophila 'mothers against decapentaplegic' (Mad) and C. elegans Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions in the negative regulation of BMP and TGF-beta/activin-signalling. Multiple transcript variants have been found for this gene.[provided by RefSeq, Sep 2014]

SMAD6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 15-66703215-C-T is Benign according to our data. Variant chr15-66703215-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1208555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-66703215-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0148 (2255/152178) while in subpopulation NFE AF= 0.0227 (1541/67974). AF 95% confidence interval is 0.0217. There are 19 homozygotes in gnomad4. There are 1015 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2255 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SMAD6	NM_005585.5 linkuse as main transcript	c.-44C>T	5_prime_UTR_variant	1/4	ENST00000288840.10	NP_005576.3
SMAD6	NR_027654.2 linkuse as main transcript	n.980C>T	non_coding_transcript_exon_variant	1/5
SMAD6	XR_931827.3 linkuse as main transcript	n.980C>T	non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD6	ENST00000288840.10 linkuse as main transcript	c.-44C>T	5_prime_UTR_variant	1/4	1	NM_005585.5	ENSP00000288840	P1	O43541-1
SMAD6	ENST00000612349.1 linkuse as main transcript	n.139C>T	non_coding_transcript_exon_variant	1/1
SMAD6	ENST00000557916.5 linkuse as main transcript		upstream_gene_variant		1		ENSP00000452955		O43541-4

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2256

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00437

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0178

Gnomad ASJ

AF:

0.0438

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00538

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0227

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.0159

AC:

541

AN:

34100

Hom.:

AF XY:

0.0150

AC XY:

275

AN XY:

18354

show subpopulations

Gnomad AFR exome

AF:

0.00659

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.0496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00282

Gnomad FIN exome

AF:

0.00731

Gnomad NFE exome

AF:

0.0233

Gnomad OTH exome

AF:

0.0248

GnomAD4 exome

AF:

0.0203

AC:

23628

AN:

1166202

Hom.:

314

Cov.:

AF XY:

0.0197

AC XY:

11152

AN XY:

565456

show subpopulations

Gnomad4 AFR exome

AF:

0.00264

Gnomad4 AMR exome

AF:

0.0146

Gnomad4 ASJ exome

AF:

0.0437

Gnomad4 EAS exome

AF:

0.0000371

Gnomad4 SAS exome

AF:

0.00169

Gnomad4 FIN exome

AF:

0.00839

Gnomad4 NFE exome

AF:

0.0223

Gnomad4 OTH exome

AF:

0.0204

GnomAD4 genome

AF:

0.0148

AC:

2255

AN:

152178

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1015

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00436

Gnomad4 AMR

AF:

0.0177

Gnomad4 ASJ

AF:

0.0438

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00538

Gnomad4 NFE

AF:

0.0227

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0162

Hom.:

Bravo

AF:

0.0153

Asia WGS

AF:

0.00145

AC:

AN:

3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 29, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over